Use of the TIPS Technique as a Possible Method of Acute Inhalation Toxicity Assessment

Acute inhalation toxicity studies provide crucial information regarding short-term exposure to volatile chemicals and help to ensure the safe handling and use of these chemicals. However, acute inhalation toxicity assessment requires specialized equipment, and most animal facilities are not able to carry out such studies. Consequently, an extremely large number of chemicals remain unassessed. Therefore, we investigated intra-Tracheal Intra-Pulmonary Spraying (TIPS) as a method for testing the acute inhalation toxicity of volatile chemicals. TIPS does not require specialized equipment and consequently is an approach that can be used by essentially all animal facilities. We diluted 12 chemicals in physiological saline and administered the chemicals to test animals using TIPS. When the acute LD50 values obtained by TIPS were converted to LC50 values, there was good agreement between the TIPS LC50 values and the reported inhalation LC50 values of nine of 11 water-soluble chemicals. Two water-soluble chemicals had TIPS LC50 values that were more than 2.5-fold higher than the published inhalation LC50 values, and water-insoluble xylene had an LC50 value that was more than 2.5-fold lower than the published inhalation LC50 value. This strong agreement between TIPS LC50 values and published LC50 values suggests that TIPS has the potential to be used for acute inhalation toxicity testing. However, further studies are needed to establish testing systems that will identify solutes that can and cannot be used for TIPS testing of different water-soluble chemicals and for TIPS testing of water-insoluble chemicals.